The yeast Schizosaccharomyces pombe (hereinafter referred to as S. pombe) is phylogenetically quite different from the budding yeast. It is greatly different from other yeasts in the chromosomal structure and the mechanisms of genome replication, RNA splicing, transcription, post-translational modification and the like and is rather analogous to animal cells in some of these mechanisms. Therefore, it is widely used as a model eukaryote (Non-patent Document 1).
Because of its various characteristics, S. pombe is considered as a unicellular eukaryote closer to higher animal cells and is a very useful yeast as a host for expression of foreign genes, especially genes from higher animals. In particular, it is known to be suitable for expression of genes from animals such as human (Patent Documents 1 to 7).
For expression of a heterologous protein in S. pombe hosts, it is required that a promoter directs transcription of foreign genes encoding the heterologous protein. As the promoter, endogenous promoters for S. pombe genes and promoters from other organisms or viruses have been used. As promoters presently used for expression of heterologous proteins in S. pombe hosts, gene promoters such as the endogenous ad1 promoter in S. pombe (for constitutive expression), the fbp1 promoter, the inv1 promoter (repressible by glucose: Patent Document 5), the ctr4 promoter (repressible by copper ions) and the nmt1 promoter (repressible by thiamine) and virus promoters such as the hCMV, SV40, CaMV promoters (for constructive expression) are known.
Patent Document 1: JP-B-2776085
Patent Document 2: JP-A-07-163373
Patent Document 3: WO96/23890
Patent Document 4: JP-A-10-234375
Patent Document 5: JP-A-11-192094
Patent Document 6: JP-A-2000-136199
Patent Document 7: JP-A-200-262284
Non-patent Document 1: Giga-Hama and Kumagai, eds., Foreign gene expression in fission yeast Schizosaccharomyces pombe, Springer-Verlag, (1997)